According to the American Cancer Society about one of every five deaths from all causes in the United States is from cancer. Although chemotherapy has become one of the principal methods of treating cancer, the rate at which drugs have become available for use in cancer chemotherapy has declined in recent years as reported by Horowitz, et al. "Phase II Testing of Melphalan in Children with Newly Diagnosed Rhabdomyosarcoma: A Model for Anticancer Drug Development", Journal of Clinical Oncology, Vol. 6, No. 2, pp. 308-314 (1988). Accordingly, there is a substantial need for new drugs which are effective in inhibiting the growth of tumors.
To be particularly useful, a new chemotherapeutic agent should have a wide spectrum of activity, a large therapeutic index, and be chemically stable and compatible with other agents. Additionally, it would be beneficial for the new agent to have oral activity so that initial treatment and subsequent maintenance therapy is more convenient and less traumatic to the patient.
It has now been found that certain N-phenyl-N'-trisubstitutedphenyl sulfonylureas are useful in the treatment of solid tumors.
Some N,N'-diarylsulfonylureas have been reported as being active antitumor agents, e.g., U.S. Pat. No. 4,845,128 of Harper, et al. (1989) and Grindey, et al. Proceedings American Association of Cancer Research, Vol. 27, pp. 277 (1986). Other N,N'-diarylsulfonylureas have also been disclosed as useful in treating tumors, i.e., EPO 222,475 and EPO 291,269 There is no suggestion in these references of the N-phenyl-N'-substitutedphenylsulfonylureas of the instant application or that these compounds whould be useful as antitumor agents.
None of these references suggest or disclose the antitumor activity of the sulfonylurea compounds of the instant invention. Additionally, there is no suggestion or disclosure of the claimed compounds of the instant invention.